Imazalil (Enilconazole)

Imazalil is an imidazole fungicide that inhibits ergosterol biosynthesis.¹ Imazalil inhibits the growth of various fungi in vitro including P. italicum, A. niger, U. maydis, B. alii, and C. cucumerinum in a pH-dependent manner (MICs = 0.005-2 μg/ml at pH 7).² It inhibits S. cerevisiae, but not rat liver microsomal, cytochrome P450 enzymes (CYPs; IC₅₀s = 0.088 and 80 μM, respectively), as well as aromatase CYP19 from human placental microsomes (IC₅₀ = 0.34 μM).^1,3 Imazalil activates the murine pregnane X receptor (PXR) in a concentration-dependent manner in a cell-based reporter assay.⁴ It increases hepatic CYP3A11 and CYP2B10 mRNA levels in mice when administered at a dose of 100 mg/kg. Imazalil also increases Ki-67-positive nuclei in liver sections and hepatic MCM2 mRNA levels, markers of cell proliferation, in mice when co-administered with the murine constitutive androstane receptor (mCAR) agonist TCPOBOP . Formulations containing imazalil have been used to control fungal infection in agriculture.

1.Vanden Bossche, H., Lauwers, W., Willemsens, G., et al.Molecular basis for the antimycotic and antibacterial activity of N-substituted imidazoles and triazoles: The inhibition of isoprenoid biosynthesisPestic. Sci.15(2)188-198(1984) 2.Siegel, M.R., Kerkenaar, A., and Kaars Sijpesteijn, A.Antifungal activity of the systemic fungicide imazalilNeth. J. Pl. Path.83(Suppl. 1)121-133(1977) 3.Vinggaard, A.M., Hnida, C., Breinholt, V., et al.Screening of selected pesticides for inhibition of CYP19 aromatase activity in vitroToxicol. In Vitro14(3)227-234(2000) 4.Yoshimaru, S., Shizu, R., Tsuruta, S., et al.Acceleration of murine hepatocyte proliferation by imazalil through the activation of nuclear receptor PXRJ. Toxicol. Sci.43(7)443-450(2018)